In 2014, an estimated 233,000 new cases of prostate cancer (PCa) were diagnosed in the US alone. Studies have shown that it is necessary to treat many men to prevent one death from PCa and that significant overtreatment exists. Even so, PCa caused an estimated 29,480 mortalities in 2014 alone. This data underscores the need for more specific PCa screening tests and more reliable PCa diagnosis at biopsy.
Systematic, untargeted prostate biopsy is the current gold standard for PCa diagnosis. Ideally, the goal is to uniformly distribute the biopsy cores according to an extended sextant biopsy plan. But a coordinate based geometric definition of the biopsy plan is typically unavailable. Rather, current biopsy plans are simplistically represented by a two dimensional (2D) cross-section of the gland showing a grid of points. This leaves room for subjective interpretation. Moreover, the number and length of the biopsy cores are not typically optimized for individual patients.
The most common way of diagnosing PCa is the transrectal ultrasound (TRUS) guided prostate biopsy. More than 1 million procedures are performed each year in the United States and Europe. While targeted biopsy methods (currently using ultrasound to magnetic resonance imaging (MRI) fusion) are being investigated for high risk patients, the most numerous, primary biopsies are still performed based on TRUS guided systematic extended sextant biopsy plans that are supposed to sample the gland uniformly. However, clinical data shows that systematic biopsies have low sensitivity and low negative predictive value. Studies have confirmed that biopsy samples are often clustered and miss regions, leading to both over- and under-sampled regions of the prostate, which increase the likelihood of detecting insignificant cancer and obtaining false negative biopsy results. Among other factors such as manual execution errors, biopsy planning is a major cause of unreliable prostate biopsy localization.
The current systematic extended sextant plans are poorly defined from a geometric standpoint. The typical 12-core extended sextant biopsy is to uniformly sample at Left/Right×Medial/Lateral×Apex/Mid/Base of the prostate. The current representation of the plan is a schematic of a grid of points on a 2D coronal section of the prostate. The basic and extended sextant plans, for example, are shown in FIG. 1A and FIG. 1B. This definition is vague, lacking the coordinate location of the cores and leaving much room for subjective interpretation. In 3D the uncertainty widens, as exemplified in FIG. 1C. It is unclear where the plane of grid should be, or whether the cores should be coplanar.
An optimal biopsy plan should be defined by 1) the number of cores and 2) core coordinate locations and directions. Several studies have been conducted to compare different number of cores (e.g. 6, 8, 12, 14, 20 cores), locations (e.g. additional cores in the apex), and directions (e.g. more lateral). Meanwhile, the American Urological Association (AUA) has recommended to use the 12-core extended sextant plan with apical and far-lateral locations of the gland, based on a literature review of clinical results.
However, other authors have reported mixed results, for example different detection rates for the same number of cores and higher detection rate with fewer cores. Possible reasons of this inconsistency may be due to patient selection differences in core placement between urologists for the same biopsy plan, and low repeatability of biopsy even for the same urologist. Moreover, false-negative biopsy rates could not be evaluated in these studies since the reference tests were based on radical prostatectomy specimens, suggesting that the true PCa detection rate could be even lower.
Biopsy plans are not typically customized for individual patients. The only parameter that may sometimes change the biopsy plans is the prostate volume. Yet it remains unclear if and how the biopsy plan should be adjusted for different prostate volume and the 12-core plan remains commonly used regardless of the volume. It was, however, suggested that since there is large variation in prostate volumes (from 10 cm3 to hundreds of cm3) biopsy core numbers need to be adjusted accordingly. Yet, other clinical studies found that there is no advantage on increasing the number of cores for larger prostates, leaving the debate still open.
Computer simulated biopsy studies have been performed based on statistical atlases using whole mount prostates. In these studies, the detection rates of different biopsy plans were measured by calculating the number of tumors detected by the simulated biopsy cores, and the number of tumors missed in each case. These groups have been first to propose and implement analytical prostate biopsy optimizations by precisely calculating the number of cores needed to achieve a certain detection rate. Among them, results were somewhat different possibly due to different statistical maps of tumor occurrence used by each group, or different placement of the cores for the same biopsy plan. Because the methods were used on the resected gland, they could not consider the path of needle insertion.
Other previous approaches used 2D analyses to determine the probability of significant cancer detection for transperineal biopsy using a grid template of equally spaced holes. This probability is calculated based on the area covered by the cores per unit grid on the transversal 2D cross section. The study demonstrated the ability to precisely calculate the probability based on prostate geometry and was able to predict the probability of a false negative result for an individual patient.
It would therefore be advantageous to provide a method that improves tumor detection probability of a given biopsy plan.